Identifying population-level relationships between predators and their prey is often predicated on having reliable population estimates. Camera-trapping is effective for surveying terrestrial wildlife, but many species lack individually unique natural markings that are required for most abundance and density estimation methods. Analytical approaches have been developed for producing population estimates from camera-trap surveys of unmarked wildlife; however, most unmarked approaches have strict assumptions that can be cryptically violated by survey design characteristics, practitioner choice of input values, or species behavior and ecology. Using multi-year datasets from populations of an unmarked predator and its co-occurring unmarked prey, we evaluated the consequences of violating two requirements of the random encounter model (REM), one of the first developed unmarked methods. We also performed a systematic review of published REM studies, with an emphasis on predator–prey ecology studies. Empirical data analysis confirmed findings of recent research that using detections from non-randomly placed cameras (e.g., on trails) and/or borrowing movement velocity (day range) values caused volatility in density estimates. Notably, placing cameras strategically to detect the predator, as is often required to obtain sufficient sample sizes, resulted in substantial density estimate inflation for both the predator and prey species. Systematic review revealed that 91% of REM density estimates in published predator–prey ecology studies were obtained using camera-trap data or velocity values that did not meet REM requirements. We suggest considerable caution making conservation or management decisions using REM density estimates from predator–prey ecology studies.